Mechanobiology of Osteoarthritis: Interactions Between Mechanical Stress, Inflammation, and Joint Remodeling

Abstract

Osteoarthritis (OA) is a multifactorial whole joint disease characterized by cartilage degeneration, subchondral bone remodeling, synovial inflammation, and progressive functional impairment. Increasing evidence suggests that OA is not simply a wear and tear disorder, but a mechanobiological disease in which abnormal mechanical stress interacts with inflammatory and metabolic pathways to drive joint degeneration. This review summarizes recent advances in the mechanobiology of OA, focusing on the interplay between mechanical stress, inflammation, and joint remodeling. We discuss the major mechanosensing and mechanotransduction mechanisms in chondrocytes, including primary cilia, integrins, the cytoskeleton, the LINC complex, and mechanosensitive ion channels such as TRPV4, TRPM7, and PIEZO channels. We further examine how these pathways regulate extracellular matrix homeostasis, chondrocyte fate, and the transition from anabolic maintenance to catabolic degeneration, as well as how altered joint loading affects subchondral bone remodeling through osteocyte responses, the RANK/RANKL/OPG axis, and Wnt/β-catenin signaling. Particular attention is given to the crosstalk between mechanotransduction and inflammatory signaling, including NF-κB, MAPK, and macrophage polarization pathways, which together amplify structural damage under pathological loading. Finally, we highlight emerging therapeutic strategies based on biomechanical modulation and mechano-inflammatory targeting. A better understanding of these integrated mechanisms may provide new insight into OA pathogenesis and support the development of disease-modifying therapies.